Treating Patients With Multiple Myeloma in the VA
Moderator
João Ascensão, MD, PhD, is a professor in the Department of Medicine and Immunology at George Washington University School of Medicine and chief hematologist and chairman of the R&D Committee at the Washington DC VA Medical Center, both in Washington, DC. He is also a clinical professor of medicine at Uniformed Services University in Bethesda, Maryland. In 2015 Dr. Ascensão served as president of the Association of VA Hematology/Oncology (AVAHO).
Panelists
Thomas R. Chauncey, MD, PhD, is an associate professor of medicine and oncology at the University of Washington, and an associate member of the Fred Hutchinson Cancer Research Center. Dr. Chauncey is director of the Marrow Transplant Unit at the VA Puget Sound Health Care System, all in Seattle.
Sean Cosgriff, PharmD, BCOP, is the hematology/oncology clinical specialist at the VA Portland Health Care System and affiliate faculty at Oregon State and Pacific University, both in Portland, Oregon. In 2014 Dr. Cosgriff served as AVAHO president.
Paulette Mehta, MD, MPH, is a professor of hematology/oncology at the University of Arkansas and a physician at the Central Arkansas Veterans Healthcare System, both in Little Rock. In 2010, Dr. Mehta served as AVAHO president.
G. David Roodman, MD, PhD, is the Kenneth Wiseman professor of medicine and director of the hematology/oncology department at Indiana University School of Medicine. Dr. Roodman is also a staff physician at the Roudebush VA Hospital Healthcare System in Indianapolis.
Nikhil C. Munshi, MD, is a professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, both in Boston, Massachusetts. Dr. Munshi is also a staff physician at the VA Boston Healthcare System at the Jamaica Plain Campus.
Dr. Ascensão. At the Washington DC VAMC in our first cycle it is day 1, 4, 8, and 11 with bortezomib, but after that we go pretty much to weekly bortezomib. We also tend to use what I would call lower dose 20 mg dexamethasone in patients over the age of 70 years. And we feel that it is a lot less toxic. We use subcutaneous bortezomib for pretty much everybody else.
Managing Adverse Effects
Dr. Chauncey. I think we’re all using subcutaneous bortezomib at this point. Dexamethasone doesn’t get a lot of independent attention, but there’s no question that, as Dr. Mehta mentioned, the older regimen that we used, the dose-dense dexamethasone of the VAD regimen, was
quite disabling. In addition to obvious hyperglycemia, there were psychiatric problems and, ultimately, profound steroid myopathy that seemed to affect patients in variable fashion. Different patients seem to be more or less susceptible, but after a couple of cycles, it starts to kick in and is progressive.
So we’ve since abandoned those massive doses. But when you look at the ECOG study (E4A03) that really defined the lower dose (40 mg weekly), there’s no question the higher dose was more toxic but also more effective in terms of disease response. While there are many older patients that I would start with a lower dose of dexamethasone, whether it’s with lenalidomide or bortezomib, I keep in mind there can be a steep dose response curve for dexamethasone. If you’re giving 20 mg and you’re not getting the response you need, then you increase the dose. There is definitely a dose response, but the higher doses are just not as well tolerated.
Dr. Cosgriff. I don’t know if other institutions are doing it, but instead of doing 40 mg as a single dose because of patient performance status, providers in Portland will prescribe 20 mg on days 1, 2, 8, 9, 15, and 16. They’ll break up that 40 mg dose and give it that way.
Dr. Chauncey. I don’t know if that strategy is biologically equivalent in terms of antimyeloma activity or less toxic in terms of myopathy. There’s almost always some disease marker to track, so that whether you’re using the serum free-light chain assay or serum protein electrophoresis, you can see if the strategy you’re using is working in real time.
Dr. Cosgriff. I’ve never known whether it’s been shown to be more efficacious or if it’s just a way of getting around some of the adverse effects. However, it does pose some alternate challenges. With higher doses of steroids, you’re looking at 2 days where the patient can become hyperglycemic, if not, a little bit longer.
The other thing with it is that adding on that extra day of dexamethasone can interfere with some other drugs and some other therapies. In individuals who have had a deep vein thrombosis for whatever reason and they’re on warfarin, now we have an agent that really screws up our warfarin monitoring. We would have to consider switching them to another agent.
Thrombosis
Dr. Mehta. It’s also prothrombotic.
Dr. Chauncey. If you actually ask the patient, independent of the hyperglycemia, independent of the myopathy, independent of psychosis, but just quality of life, they’ll typically tell you that the on-and-off of steroids is the worst part of the regimen. It’s often the roller coaster ride of short-term hypomania followed by dysphoria.
Dr. Mehta. And the lack of sleep. They describe it as being out of their skin.
Dr. Chauncey. They are. And as soon as they stop, often there is a depression.
Dr. Mehta. It is very, very difficult. And some actually develop psychosis.
Dr. Ascensão. We all use some form of acyclovir or its derivative for the prevention of shingles in patients exposed to the proteasome inhibitors. We use aspirin, usually low dose (81 mg), for deep vein thrombosis prophylaxis. But is anybody using other anticoagulants or putting everybody prophylactically on proton-pump inhibitors (PPIs) or just seeing how people do first and then adjusting?
Dr. Chauncey. I typically use conventional dose aspirin, and if there’s breakthrough thrombosis, the first response should be that it is not the best regimen for this patient. Sometimes you have to go back to it, and if someone’s an anticoagulation candidate, then full anticoagulation is
needed if that’s the best regimen. Usually if there’s a breakthrough thrombosis, it is a deal breaker, and you’re ready to move on to a nonthrombogenic regimen.
There has been an observation (there is some biological basis to back this up) that if you give bortezomib with an IMiD, the regimen became less thrombogenic than with the IMiD and dexamethasone alone.
Dr. Ascensão. On aspirin, even if they’re on an IMiD plus a proteasome inhibitor, I just don’t know that the data are good enough for us to avoid it at this point in time. And I don’t necessarily put people on a PPI unless they’ve got added gastrointestinal problems and unless they have associated heartburn or dyspepsia symptoms.
Dr. Mehta. I use low-dose aspirin in every patient. And if they breakthrough, they go on full anticoagulation usually with a new oral anticoagulant. I use PPIs only if needed, although most of them do need it, and, of course, bisphosphonates so the bone protective aspect.
